Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.

Objective To observe the parameters and effect of endocardial pacing by steel wire electrode cardiac puncture on heart with normal beat in living animal, and evaluate its safety.Methods After anaesthesia and thoracotomy in 6 living dogs with normal heart beat, the pericardia were excised. Steel wire electrodes with annular or hook tips were used respectively at right ventricular 4 corresponding spots to perform cardiac puncture endocardiac pacing (each dog experienced 8 times of puncture); the time from puncture to effective pacing, pacing parameter and puncture complication (time and quantity of bleeding) of each electrode at each spot were recorded. Finally, the two types of electrode completed 24 times of manipulation respectively; the data collected of the two types were compared. Results The cardiac pacing successful rates in the two groups were 100%; the time taken from the beginning of heart puncture to effective pacing in annular tip group was less than that in hook tip group, but the time difference between the two groups showed no statistical significance (s: 18.4±2.3 vs. 19.6±4.1,P > 0.05). The parameters of pacing in the annular tip group, such as operation time (s: 18.4±2.3 vs. 19.6±4.1), the threshold value of pacing (V: 2.1±0.2 vs. 2.2±0.8), the amplitude of R wave sensed (mV: 11.3±3.2 vs. 12.6±4.1) and the impedance of electrode (Ω: 674.2±89.7 vs. 668.5±101.3) were not significantly different compared with those in the hook tip group (allP > 0.05). Either after puncture or after the electrodes were taken out, the time of bleeding [after puncture (minutes): 4.4±2.3 vs. 4.5±3.1, after the electrodes taken out (minutes): 4.1±2.2 vs. 4.8±2.5] and the volume of bleeding [after puncture (mL): 2.8±2.4 vs. 3.2±3.5, after the electrodes taken out (mL): 3.3±1.7 vs. 3.5±2.6] were not significantly different between the two groups (allP > 0.05).Conclusions In living dogs with normal heart beat, the manipulation and function of endocardiac pacing by cardiac puncture with either steel wire annular or hook tip electrode are well and effective, and the performance is simple and safe without any serious myocardial injury and complication. Thus, it is helpful to quickly establish efficient endocardiac pacing in emergency cases.

OBJECTIVETo study the combination of Mandibular distraction and orthognathic techniques for the reconstruction of adult hemifacial microsomia.

METHODSThe three-dimensional CT reconstruction data was used with Mimics for preoperation design. The osteotomy location, distraction vector, distraction distance were decided before operation with a surgical guider. At the first stage, internal distractor was implanted after ostetomy through an extra-oral approach. The distraction begun 5-7 days after operation with a frequency of 1 mm/day. After distraction, the distractor was maintained for 3-6 months. At the second stage, the distractor was removed. Le Fort I osteotomy was performed in order to correct the cross-bite and improve the facial contour. Usually, bone graft was inserted into the gap after Le Fort I osteotomy. The genioplasty was also performed if necessary.

RESULTS9 cases of adult hemifacial microsomia with severe mandibular deviation were treated. The facial asymmetry were improved greatly. 1 patient suffered an wound infection in the maxillary region after Le Fort I osteotomy and healed uneventfully with wound irrigation.

CONCLUSIONSMandibular distraction combined with orthognathic surgery is an effective procedure for adult hemifacial microsomia with complicated mandibular hypoplasia.

Adult ; Aged ; Bone Transplantation ; Facial Asymmetry ; surgery ; Goldenhar Syndrome ; surgery ; Humans ; Mandible ; surgery ; Osteogenesis, Distraction ; methods ; Osteotomy, Le Fort ; methods

Biliary Atresia ; diagnosis ; etiology ; therapy ; Bilirubin ; blood ; Biomarkers ; blood ; Calcium-Binding Proteins ; deficiency ; Cholangiopancreatography, Magnetic Resonance ; Cholestasis, Intrahepatic ; diagnosis ; etiology ; therapy ; Citrullinemia ; diagnosis ; etiology ; therapy ; DNA Mutational Analysis ; Humans ; Infant ; Jaundice ; diagnosis ; etiology ; therapy ; Liver Function Tests ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation ; Organic Anion Transporters ; deficiency

OBJECTIVE: By observing the cerebral beta-amyloid precursor protein (beta-APP) expression in the chronic alcoholism rats with slight cerebral injury, to discuss the correlation of chronic alcoholism and death caused by traumatic subarachnoid haemorrhage (TSAH). METHODS: Sixty male SD rats were randomly divided into watering group, watering group with strike, alcoholism group and alcoholism group with strike. Among them, the alcohol was used for continuous 4 weeks in alcoholism groups and the concussion was made in groups with strike. In each group, HE staining and immunohistochemical staining of the cerebral tissues were done and the results were analyzed by the histopathologic image system. RESULTS: In watering group, there was no abnormal. In watering group with strike, mild neuronic congestion was found. In alcoholism group, vascular texture on cerebral surface was found. And the neurons arranged in disorder with dilated intercellular space. In alcoholism group with strike, diffuse congestion on cerebral surface was found. And there was TSAH with thick-layer patches around brainstem following irregular axonotmesis. The quantity of beta-APP IOD in alcoholism group was significantly higher in the frontal lobe, hippocampus, cerebellum, brainstem than those in watering group with strike and alcoholism group with strike. CONCLUSION The cerebral tissues with chronic alcoholism, due to the decreasing tolerance, could cause fatal TSAH and pathological changes in cerebral tissues of rats under slight cerebral injury.
Alcoholism/pathology* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Brain/pathology* ; Brain Concussion/pathology* ; Disease Models, Animal ; Ethanol/adverse effects* ; Male ; Neurons/pathology* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage, Traumatic/pathology*

BACKGROUNDIt has been 11 years since newborn screening started in Zhejiang in 1999. The aim of this study was to analyze and summarize the status of newborn screening in Zhejiang from 1999 to 2009.

METHODSBlood samples were collected from the heels of newborns 72 hours after birth. We have conducted laboratory tests that the congenital hypothyroidism (CH) and circulating levels of thyroid-stimulating hormone (TSH) was detected. Blood phenylalanine (Phe) was detected for phenylketonuria (PKU). Dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) was used for detection.

RESULTSFrom 1999 to 2009, 3 875 228 newborns were screened and 2309 cases were confirmed as CH and 155 cases were confirmed as PKU. The incidence of CH and PKU were 1:1678 and 1:25 001 respectively.

CONCLUSIONIn 11 years, the Zhejiang newborn screening center screened more than 3.8 million newborns, and helped more than 2000 CH and PKU patients to obtain early treatment in order to prevent physical disability and mental retardation.

China ; Congenital Hypothyroidism ; diagnosis ; Humans ; Infant, Newborn ; Neonatal Screening ; methods ; Phenylketonurias ; diagnosis

BACKGROUNDVelvet antler polypeptides (VAPs), which are derived from the antler velvets, have been reported to maintain survival and promote growth and differentiation of neural cells and, especially the development of neural tissues. This study was designed to explore the influence of VAPs on neural stem cells in vitro derived from embryonic rat brain.

METHODSNeural stem cells derived from E12-14 rat brain were isolated, cultured, and expanded for 7 days until neural stem cell aggregations and neurospheres were generated. The neurospheres were cultured under the condition of different concentration of VAPs followed by immunocytochemistry to detect the differentiation of neural stem cells.

RESULTSVAPs could remarkably promote differentiation of neural stem cells and most neural stem cells were induced to differentiate towards the direction of neurons under certain concentration of VAPs.

CONCLUSIONNeural stem cells can be successfully induced into neurons by VAPs in vitro, which could provide a basis for regeneration of the nervous system.

Animals ; Antlers ; chemistry ; Brain ; embryology ; Cell Differentiation ; Cells, Cultured ; Dose-Response Relationship, Drug ; Glial Fibrillary Acidic Protein ; analysis ; Immunohistochemistry ; Nerve Growth Factors ; pharmacology ; Neurons ; cytology ; Peptides ; pharmacology ; Rats ; Rats, Wistar ; Stem Cells ; cytology ; drug effects

OBJECTIVETo study the absorption, translocation and accumulation of N, P and K on Achyranthes bidentata.

METHODThe contents of N, P and K were determined by mean of sulfuric acid-hydrogen peroxide assimilating method, vanadium-ammonium molybdate colorimetric method and flame photometric method, respectively.

RESULTThe contents of N, P and K in the plant were decreasing during the growth period. The absorption rates of the three nutrients by A. Bidentata showed double-peak curves in the whole growth period, maximum absorption rate appeared in the middle ten days of October. About 8.59 kg of N, 1.36 kg of P and 7.40 kg of K were needed to produce each 100 kg root.

CONCLUSIONThe key nutrients absorption period is in the first ten days of September and in the middle ten days of October.

Achyranthes ; metabolism ; Biological Transport ; Nitrogen ; metabolism ; Phosphorus ; metabolism ; Potassium ; metabolism

OBJECTIVETo explore a new method to treat brachial plexus root avulsion experimentally by reimplantation combined with transplantation of neural stem cells (NSCs) modified by neurotrophin-3 gene (NT-3).

METHODSThe total RNA was extracted from neonatal rat striatum and the NT-3 cDNA was obtained by reverse transcription and amplified by polymerase chain reaction. The NT-3 gene was transferred into NSCs via the pLEGFP-C1, an expression plasmid vectors. The untransfected NSCs, the pLEGFP-C1 treated NSCs, and the pLEGFP-C1-NT-3 treated NSCs were transplanted into corresponding spinal cord segment with brachial plexus root avulsion. The survival, differentiation, and migration of the transplanted cells were determined under confocal laser scanning microscope or by immunohistochemistry method. The nerve regeneration was evaluated by gross observation, electrophysiological examination and reverse horseradish peroxidase tracing.

RESULTSThe NT-3 gene was successfully amplified and transferred into neural stem cells via the plasmid vectors. The transplanted cells survived, differentiated, and migrated and NT-3 was expressed within the spinal cord. The animals regained some muscle strength which was less than 3-degree muscular strength according to the British Medical Research Council (BMRC) evaluating system. The results of electrophysiological examination and reverse horseradish peroxidase tracing were superior in the pLEGFP-C1-NT-3 group to the NSCs untransfected group or the pLEGFP-C1 group.

CONCLUSIONTransplantation of NSCs modified by NT-3 gene combined with reimplantation is a relatively effective way to treat brachial plexus root avulsion experimentally. It still need further study to improve the results.

Animals ; Brachial Plexus ; injuries ; Neurotrophin 3 ; genetics ; Radiculopathy ; surgery ; Rats ; Replantation ; Stem Cell Transplantation ; Transfection

Objective To explore a training system of high level professionals with international vision and meeting the develop-ment of assistive technology in China. Methods The training system was constructed in the theory framework of International Classification of Functioning, Disability and Health,and work process-oriented. Results and Conclusion A curriculum system with tree-type modes and a practice system with three-level and multi-form of assistive technology specialty were constructed,that was recognized by industry and society in the developing.